Tuesday, October 5, 2010

Explaining the germ cell cancer rates

In yesterday's blog we explained how the precancer of testicular germ cell tumors, intratubular germ cell neoplasia, gives rise to seminomas (differentiated germinomatous lineage) and non-seminomas (tumors of pluripotent progenitor cells that are not of germ cell lineage).

In the first blog of this series on germ cell tumors , we noted that the increase in occurrences of seminomas has outpaced the occurrences of the nonseminomatous germ cell tumors.

Here is a graph, produced from the SEER public use data sets, of the crude occurrences of seminoma and non-seminoma testicular germ cell tumors, in white males, since 1973.

The light blue bars are the seminomas, and the maroon bars are the non-seminomatous germ cell tumors of the testes. Since 1973, the seminomas increased from a number much lower than the occurrences of the non-seminomatous germ cell tumors; exceeding them in 1977. Since 1977, the crude occurrences of seminomas has greatly outpaced the occurrences of the non-seminomatous germ cell tumors of testes in white males.

Why? If both types of tumors are coming from the same precancer, why are their trends of occurrence non-parallel?

Well, there are several possible answers. It is possible that some external influence has modified the step in the progression of precancer to cancer, to favor the occurrence of seminomas.

However, it is also possible that their increases in occurrence are indeed parallel, and we're just not seeing it in our graph. Bray et al have looked at the incidence of testicular seminoma and non-seminoma germ cell tumors, by cohort (i.e., year of birth), not by year of occurrence.[1]

Bray F, Richiardi L, Ekbom A, Forman D,Pukkala E, Cuninkova M, Moller H. Do Testicular Seminoma and Nonseminoma Share the Same Etiology? Evidence from an Age-Period-Cohort Analysis of Incidence Trends in Eight European Countries. Cancer Epidemiol Biomarkers Prev 15:652–658, 2006.

When the comparisons are based on cohort (comparing incidence for people born the same year), most of the differences vanish [between the incidence of seminomas and non-seminomatous germ cell tumors].

When do we see a birth corhort effect on tumor incidence? For cancers, a cohort effect is best observed when individuals born in one year are exposed (as a population group) to a causal agent that is different from the exposure of individuals born in other years. The cancers that result may occur at many different ages, thus erasing the cohort effect when the data is stratified by year of occurrence (as we had done the graph above). Only when you look at the birth cohort will you find a trend that may relate to a carcinogenic exposure.

OK. The birth cohort data reported by Bray et al would seem to indicate that some generational effect is acting on succeeding cohorts to produce a shared increase in the incidence of all testicular germ cell cancers. Furthermore, whatever is causing the generational effect is likely to be of short duration or differ significantly from year to year. Why is that? If the exposure of a carcinogen were of long duration or were the same from year to year, then every cohort would be exposed similarly, and there would be no birth-year specific effect.

So, now the mystery is: What are the conditions and carcinogens that might cause testicular germ cell tumors, which have changed, year-by-year, to produce the observed rise in these cancers in white males? This will be the topic of the next blog.

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- © 2010 Jules Berman

key words: carcinogenesis, neoplasia, neoplasms, tumor development, tumour development, germ cell tumor, germ cell tumour, tumor epidemiology, increasing germ cell cancer rates, germ cell cancer, seminomas, seminomatous, non-seminomatous, non-germinomatous, embryonal carcinoma, choriocarcinoma, testis, testes, itgcn, intratubular germ cell neoplasm
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